DESCRIPTION (From the Applicant's Abstract): This application will investigate the mechanisms by which oligodendrocytes progress from a proliferating precursor cell to a fully myelinating cell. It is well established that oligodendrocytes can myelinate multiple axons in the central nervous system. The appearance of oligodendrocytes and their ability to undergo myelination in the CNS occur relatively late during development, after neurogenesis. A number of components of the myelin sheath have been identified, but the underlying molecular mechanisms that control myelin formation and oligodendroglial cells numbers are not fully understood. The specific aims will focus upon the contribution of the cell cycle machinery on the regulation of oligodendrocyte proliferation. In addition, signal transduction events through Fyn tyrosine phosphorylation have been found to be one of the earliest events during oligodendrocyte differentiation. The major objectives will be to define how cell cycle regulation leads to cell specification and how activation of tyrosine kinase activities promotes oligodendrocyte process formation and myelination. These studies may eventually lead to the identification of signals required for oligodendrocytes to form an insulating myelin sheet around axons in the nerve. This investigation will have a direct impact upon basic mechanisms affecting CNS regeneration, remyelination and demyelinating diseases, such as multiple sclerosis.